Noninvasive Imaging and Monitoring of Retinal Pigment Epithelium Patterns Using Fundus Autofluorescence - Review

Non-invasive imaging of the retinal pigment epithelium (RPE) using autofluorescence became recently available with the introduction of confocal laser scanning ophthalmoscopes. Fundus autofluorescence is usually excited at a wavelength of 488nm and the emitted light is detected above 500nm. This intrinsic autofluorescence was shown to derive from the lipofuscin accumulating within the RPE either with age or also due to different hereditary or degenerative diseases of the macula as e.g. age-related macular degeneration. Since a variety of macular diseases correlate with distinct RPE changes, specific patterns of autofluoresce nce could be evaluated within the recent years for diagnostic and prognostic reasons in those RPE-related diseases. Moreover autofluorescence can also be regarded as a monitoring tool after therapeutic applications as macular surgery or laser treatment. Other new applications try to determine macular pigment density using autofluorescence or use it to evaluate oxygen-dependent cell metabolism. This review summarizes the recent findings of autofluoresce nt patterns in specific diseases and therapeutic approaches and emphasizes on the tremendous potential of this novel imaging method.

[1]  I. Wallow.  Repair of the pigment epithelial barrier following photocoagulation. , 1984, Archives of ophthalmology.

[2]  J. Weiter,et al.  Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration. , 1989, Investigative ophthalmology & visual science.

[3]  F W Fitzke,et al.  In vivo fundus autofluorescence in macular dystrophies. , 1997, Archives of ophthalmology.

[4]  F. Delori,et al.  Lipofuscin in Aged and AMD Eyes , 1993 .

[5]  Jürgen Kopitz,et al.  Isolation of intact lysosomes from human RPE cells and effects of A2-E on the integrity of the lysosomal and other cellular membranes , 2002, Graefe's Archive for Clinical and Experimental Ophthalmology.

[6]  L. Feeney-Burns,et al.  Aging human RPE: morphometric analysis of macular, equatorial, and peripheral cells. , 1984, Investigative ophthalmology & visual science.

[7]  R Birngruber,et al.  Autofluorescence imaging after selective RPE laser treatment in macular diseases and clinical outcome: a pilot study , 2002, The British journal of ophthalmology.

[8]  S. Fine,et al.  Simulated treatment of recurrent choroidal neovascularization in primate retina. Comparative histopathologic findings. , 1985, Archives of ophthalmology.

[9]  C. Framme,et al.  Immediate and long-term changes of fundus autofluorescence in continuous wave laser lesions of the retina. , 2004, Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye.

[10]  M. Katz.  Incomplete proteolysis may contribute to lipofuscin accumulation in the retinal pigment epithelium. , 1989, Advances in experimental medicine and biology.

[11]  F Hillenkamp,et al.  Microphotocoagulation: selective effects of repetitive short laser pulses. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[12]  C K Dorey,et al.  In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics. , 1995, Investigative ophthalmology & visual science.

[13]  R. Eagle,et al.  Retinal Pigment Epithelial Abnormalities in Fundus Flavimmaculatus , 1980 .

[14]  J. Weiter,et al.  Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes. , 1986, Investigative ophthalmology & visual science.

[15]  C. Framme,et al.  RPE in Perfusion Tissue Culture and Its Response to Laser Application , 2002, Ophthalmologica.

[16]  K. Nakanishi,et al.  Isolation and one-step preparation of A2E and iso-A2E, fluorophores from human retinal pigment epithelium. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[17]  J. Folk,et al.  Acute, posterior, multifocal, placoid, pigment epitheliopathy and Lyme disease. , 1992, Archives of ophthalmology.

[18]  F. Holz.  Autofluoreszenz-Imaging der Makula , 2001, Der Ophthalmologe.

[19]  F W Fitzke,et al.  Fundus autofluorescence in age-related macular disease imaged with a laser scanning ophthalmoscope. , 1997, Investigative ophthalmology & visual science.

[20]  E. Berman,et al.  Lipofuscin of human retinal pigment epithelium. , 1980, American journal of ophthalmology.

[21]  S. Fine,et al.  Cell proliferation after laser photocoagulation in primate retina. An autoradiographic study. , 1986, Archives of ophthalmology.

[22]  W. Green,et al.  Autosomal-dominant fundus flavimaculatus. Clinicopathologic correlation. , 1990, Ophthalmology.

[23]  R Birngruber,et al.  Retinal sparing by selective retinal pigment epithelial photocoagulation. , 1999, Archives of ophthalmology.

[24]  C. Bellmann,et al.  Patterns of increased in vivo fundus autofluorescence in the junctional zone of geographic atrophy of the retinal pigment epithelium associated with age-related macular degeneration , 1999, Graefe's Archive for Clinical and Experimental Ophthalmology.

[25]  S. Beatty,et al.  Perennial Measurements of Macular Pigment Optical Density and Serum Levels of Its Constituent Carotenoids , 2004 .

[26]  C. Keilhauer,et al.  IMAGING OF RETINAL AUTOFLUORESCENCE IN PATIENTS WITH AGE‐RELATED MACULAR DEGENERATION , 1997, Retina.

[27]  M. Katz,et al.  Formation of lipofuscin-like fluorophores by reaction of retinal with photoreceptor outer segments and liposomes , 1996, Mechanisms of Ageing and Development.

[28]  Ian J Constable,et al.  Lipofuscin of the retinal pigment epithelium: A review , 1995, Eye.

[29]  D. M. Gass,et al.  Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment , 1987 .

[30]  J. Mellerio,et al.  Pathological development of retinal laser photocoagulations. , 1967, Experimental eye research.

[31]  G. Eldred,et al.  Retinal age pigments generated by self-assembling lysosomotropic detergents , 1993, Nature.

[32]  R Birngruber,et al.  Response of the retinal pigment epithelium to selective photocoagulation. , 1992, Archives of ophthalmology.

[33]  W R Green,et al.  Age-related Macular Degeneration Histopathologic Studies: The 1992 Lorenz E. Zimmerman Lecture , 1993, Ophthalmology.

[34]  W. Green,et al.  Response of pig retinal pigment epithelium to laser photocoagulation in organ culture. , 1989, Archives of ophthalmology.

[35]  M. Katz,et al.  Fluorophores of the human retinal pigment epithelium: separation and spectral characterization. , 1988, Experimental eye research.

[36]  A. Bird,et al.  Abnormalities of fundus autofluorescence in central serous retinopathy. , 2002, American journal of ophthalmology-glaucoma.

[37]  F. Delori.  Spectrophotometer for noninvasive measurement of intrinsic fluorescence and reflectance of the ocular fundus. , 1994, Applied Optics.

[38]  J. Weiter,et al.  In vivo measurement of lipofuscin in Stargardt's disease--Fundus flavimaculatus. , 1995, Investigative ophthalmology & visual science.

[39]  C Bellman,et al.  Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration. , 2001, Investigative ophthalmology & visual science.

[40]  S. Fine,et al.  A histopathologic study of Best's macular dystrophy. , 1982, Archives of ophthalmology.

[41]  R Birngruber,et al.  Subthreshold (retinal pigment epithelium) photocoagulation in macular diseases: a pilot study , 2000, The British journal of ophthalmology.

[42]  G BENNETT,et al.  Central Serous Retinopathy * , 1955, The British journal of ophthalmology.

[43]  S A Burns,et al.  Macular pigment density measured by autofluorescence spectrometry: comparison with reflectometry and heterochromatic flicker photometry. , 2001, Journal of the Optical Society of America. A, Optics, image science, and vision.

[44]  Charles P. Lin,et al.  Origin of retinal pigment epithelium cell damage by pulsed laser irradiance in the nanosecond to microsecond time regimen , 2000, Lasers in surgery and medicine.

[45]  J. Cunha-Vaz,et al.  Clinicopathologic study of blood-retinal barrier in experimental diabetes mellitus. , 1980, Archives of ophthalmology.

[46]  S. Wolf,et al.  A new instrument for the quantification of macular pigment density: first results in patients with AMD and healthy subjects , 2002, Graefe's Archive for Clinical and Experimental Ophthalmology.

[47]  N. Yoshimura,et al.  Increased production of transforming growth factor-beta 2 from cultured human retinal pigment epithelial cells by photocoagulation. , 1994, Investigative ophthalmology & visual science.

[48]  J. Marshall,et al.  A comparative histopathological study of argon and krypton laser irradiations of the human retina. , 1979, The British journal of ophthalmology.

[49]  F. Kruse,et al.  Inhibition of lysosomal degradative functions in RPE cells by a retinoid component of lipofuscin. , 1999, Investigative ophthalmology & visual science.

[50]  S. Wolf,et al.  Macular pigment density in healthy subjects quantified with a modified confocal scanning laser ophthalmoscope , 2003, Graefe's Archive for Clinical and Experimental Ophthalmology.

[51]  Paul S. Bernstein,et al.  Mutation of the Stargardt Disease Gene (ABCR) in Age-Related Macular Degeneration , 1997 .

[52]  Fred W. Fitzke,et al.  Macular pigment density and distribution: comparison of fundus autofluorescence with minimum motion photometry , 2003, Vision Research.

[53]  Reginald Birngruber,et al.  Quantifizierung der Wellenlängenabhängigkeit laserinduzierter Aderhauteffekte , 1989 .

[54]  Reginald Birngruber,et al.  Optoacoustic detection of selective RPE cell damage during μs-laser irradiation , 2001, European Conference on Biomedical Optics.

[55]  S. Fine,et al.  Comparison of krypton and argon laser photocoagulation. Results of stimulated clinical treatment of primate retina. , 1984, Archives of ophthalmology.

[56]  Z. Gregor,et al.  Fundus autofluorescence in patients with macular holes imaged with a laser scanning ophthalmoscope , 1998, The British journal of ophthalmology.

[57]  H. Sachs,et al.  Fundus autofluorescence in APMPPE in association with lyme disease. , 2002, Retina.

[58]  Dietrich Schweitzer,et al.  Basic investigations for 2-dimensional time-resolved fluorescence measurements at the fundus. , 2001 .

[59]  D. Guyer.  Retina-Vitreous-macula , 1999 .

[60]  Rinaldo Cubeddu,et al.  Age-related changes in the morphology, absorption and fluorescence of melanosomes and lipofuscin granules of the retinal pigment epithelium , 1990, Vision Research.

[61]  B. Lorenz,et al.  Lack of fundus autofluorescence to 488 nanometers from childhood on in patients with early-onset severe retinal dystrophy associated with mutations in RPE65. , 2004, Ophthalmology.

[62]  W. Heriot,et al.  Cellular processes causing defects in Bruch's membrane following krypton laser photocoagulation. , 1986, Ophthalmology.

[63]  A. Kolb,et al.  Zeitaufgelöste Messung der Autofluoreszenz , 2002, Der Ophthalmologe.

[64]  R. Birngruber,et al.  Online autofluorescence measurements during selective RPE laser treatment , 2004, Graefe's Archive for Clinical and Experimental Ophthalmology.